Mechanism of bilateral communication in the suprachiasmatic nucleus.

The central circadian pacemaker of the suprachiasmatic nuclei (SCN) is a bilaterally symmetrical structure. Little is known about the physiological mechanisms underlying communication between the left and right SCN and yet the degree of synchronization between SCN neurons can have a critical impact on the properties of the circadian system. In this study, we used electrophysiological tools and calcium (Ca(2+) ) imaging to examine the mechanisms underlying bilateral signaling in mouse SCN. Electrical stimulation of one SCN produced responses in the contralateral SCN with a short delay (approximately 5 ms) and Ca(2+) -dependence that are consistent with action potential-mediated chemical synaptic transmission. Patch-clamp recordings of stimulated cells revealed excitatory postsynaptic inward-currents (EPSCs), which were sufficient in magnitude to elicit action potentials. Electrical stimulation evoked tetrodotoxin-dependent Ca(2+) transients in about 30% of all contralateral SCN neurons recorded. The responding neurons were widely distributed within the SCN with a highest density in the posterior SCN. EPSCs and Ca(2+) responses were significantly reduced after application of a glutamate receptor antagonist. Application of antagonists for receptors of other candidate transmitters inhibited the Ca(2+) responses in some of the cells but overall the impact of these antagonists was variable. In a functional assay, electrical stimulation of the SCN produced phase shifts in the circadian rhythm in the frequency of multiunit activity rhythm in the contralateral SCN. These phase shifts were blocked by a glutamate receptor antagonist. Taken together, these results implicate glutamate as a transmitter required for communication between the left and right SCN.

Daily and seasonal adaptation of the circadian clock requires plasticity of the SCN neuronal network.

Circadian rhythms are an essential property of many living organisms, and arise from an internal pacemaker, or clock. In mammals, this clock resides in the suprachiasmatic nucleus (SCN) of the hypothalamus, and generates an intrinsic circadian rhythm that is transmitted to other parts of the CNS. We will review the evidence that basic adaptive functions of the circadian system rely on functional plasticity in the neuronal network organization, and involve a change in phase relation among oscillatory neurons. We will illustrate this for: (i) photic entrainment of the circadian clock to the light-dark cycle; and (ii) seasonal adaptation of the clock to changes in day length. Molecular studies have shown plasticity in the phase relation between the ventral and dorsal SCN during adjustment to a shifted environmental cycle. Seasonal adaptation relies predominantly on plasticity in the phase relation between the rostral and caudal SCN. Electrical activity is integrated in the SCN, and appears to reflect the sum of the differently phased molecular expression patterns. While both photic entrainment and seasonal adaptation arise from a redistribution of SCN oscillatory activity patterns, different neuronal coupling mechanisms are employed, which are reviewed in the present paper.